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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2008

01-12-2008 | Clinical Trial Report

Phase I trial of weekly trabectedin (ET-743) and gemcitabine in patients with advanced solid tumors

Authors: Wells A. Messersmith, Antonio Jimeno, David Ettinger, Dan Laheru, Julie Brahmer, Dina Lansey, Yasmin Khan, Ross C. Donehower, Yusri Elsayed, Peter Zannikos, Manuel Hidalgo

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2008

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Abstract

Purpose

To determine the maximum tolerated dose (MTD) of trabectedin plus gemcitabine administered on a weekly schedule in patients with advanced solid tumors.

Methods

Patients with ECOG performance status 0–1 and adequate organ function were enrolled. On days 1, 8, and 15 of a 28-day cycle, patients received gemcitabine (starting dose, 800 mg/m2) followed by trabectedin (starting dose, 0.3 mg/m2). Strict liver function test treatment criteria were employed to avoid hepatic toxicity seen in previous trabectedin studies. Plasma samples were collected during cycles 1 and 2 for pharmacokinetic analyses.

Results

Fifteen patients received ≥1 dose, with a median of two treatment cycles (range 1–10). The most common drug-related toxicity was hepatic. Dose reductions were required for trabectedin in four (27%) patients and gemcitabine in six (40%) patients. Cycle delays/dose holds were required in 11 (73%) patients and doses above trabectedin 0.4 mg/m2 and gemcitabine 1,000 mg/m2, which is the recommended phase II dose, were not feasible. Seven patients maintained stable disease after two cycles. Gemcitabine and trabectedin pharmacokinetics were not altered substantially with concomitant administration.

Conclusions

Given the lack of pharmacokinetic interaction and potential efficacy of trabectedin and gemcitabine combination therapy, further study is warranted with alternate schedules.
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Metadata
Title
Phase I trial of weekly trabectedin (ET-743) and gemcitabine in patients with advanced solid tumors
Authors
Wells A. Messersmith
Antonio Jimeno
David Ettinger
Dan Laheru
Julie Brahmer
Dina Lansey
Yasmin Khan
Ross C. Donehower
Yusri Elsayed
Peter Zannikos
Manuel Hidalgo
Publication date
01-12-2008
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0733-7

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